The identification of clinical and biologidal characteristics which distinguish psychotic patients with and without increased serum creatine phosphokinase (CPK) activity will be further studied in hospitalized psychiatric patients. The possibility of persistently elevated mean serum CPK activity as well as brief increases of larger magnitude will be studied. The correlation between daily fluctuations in serum CPK activity and psychopathology will be replicated. Correlations between serum CPK activity and telemetered motor activity will be studied. The usefulness of pyruvate kinase (PK) activity as a marker for muscle enzyme release in psychotic patients will be examined. Determination of serum CPK and PK levels will be carried out in first degree relatives of psychotic patients. Correlations of CPK levels in psychotic patients and first degree relatives will be studied. the heritability of serum CPK will be further explored. Spinal fluid CPK activity in psychotic patients will be investigated. Serum CPK and PK levels in patients with a variety of acute brain diseases will be studied. The effect of lithium carbonate, epinephrine, norepinephrine and serotonin on serum CPK levels in man will be studied. The effects of a cold pressor test on CPK levels in psychotic patients will be studied. A radioimmunoassay for CPK will be developed. Several possible animal models that bridge the gap between biochemical mechanisms of psychosis and muscle enzyme release will be studied. These include determining the effects on plasma CPK levels in rats, and in some instances, rabbits, of: the psychotomimetic drugs, phencyclidine and restraint stress; electrical shock to the tail; MAO inhibitors, including the hallucinogen, harmaline; amine reuptake blockers and serotonin; brain lesions and stimulation. Particular emphasis will be placed on the possible role of muscle tension, endocrine influences and Na, K ions-ATPase on muscle enzyme release. The effect of prolonged administration of drugs which affect bioamines on CPK activity will be studied. Pilot studies on plasma CPK levels in monkeys with septal lesions will be carried out.